A5062537181- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Calcium signaling and nucleotide metabolism
- Alzheimer's disease research and treatments
- Endoplasmic Reticulum Stress and Disease
- Sirtuins and Resveratrol in Medicine
- Parkinson's Disease Mechanisms and Treatments
- Cannabis and Cannabinoid Research
- Cardiac Ischemia and Reperfusion
- Hippo pathway signaling and YAP/TAZ
- Advanced Glycation End Products research
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Genomics, phytochemicals, and oxidative stress
- Cell death mechanisms and regulation
- Cholinesterase and Neurodegenerative Diseases
- Platelet Disorders and Treatments
- Cellular transport and secretion
- Redox biology and oxidative stress
- Neuroscience and Neuropharmacology Research
- Adenosine and Purinergic Signaling
- Signaling Pathways in Disease
- Toxoplasma gondii Research Studies
- Cardiac Fibrosis and Remodeling
Chungbuk National University
2022-2025
Rutgers New Jersey Medical School
2016-2025
Rutgers, The State University of New Jersey
2016-2025
Seoul National University
2008-2022
Howard Hughes Medical Institute
2016
Albert Einstein College of Medicine
2016
The University of Texas Southwestern Medical Center
2016
GE Global Research (United States)
2013
Creative Research
2008
Autophagy has been implicated in the ageing process, but whether autophagy activation extends lifespan mammals is unknown. Here we show that ubiquitous overexpression of Atg5, a protein essential for autophagosome formation, median mice by 17.2%. We demonstrate moderate Atg5 enhances autophagy, and transgenic showed anti-ageing phenotypes, including leanness, increased insulin sensitivity improved motor function. Furthermore, mouse embryonic fibroblasts cultured from are more tolerant to...
Energy stress, such as ischemia, induces mitochondrial damage and death in the heart. Degradation of damaged mitochondria by mitophagy is essential for maintenance healthy survival. Here, we show that during myocardial ischemia was mediated predominantly through autophagy characterized Rab9-associated autophagosomes, rather than well-characterized form dependent on autophagy-related 7 (Atg) conjugation system LC3. This played an role protecting heart against a protein complex consisting...
Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report identification of flavonoid 4,4'-dimethoxychalcone (DMC) as a natural compound anti-ageing properties. External DMC administration extends lifespan yeast, worms flies, decelerates senescence human cell cultures,...
Although autophagy is generally protective, uncontrolled or excessive activation of can be detrimental. However, it often difficult to distinguish death by from with autophagy, and whether contributes in cardiomyocytes (CMs) still controversial. Excessive induces a morphologically biochemically defined form cell termed autosis. Whether autosis involved tissue injury induced under pathologically relevant conditions poorly understood. In the present study, myocardial ischemia/reperfusion (I/R)...
Well-controlled mitochondrial homeostasis, including a mitochondria-specific form of autophagy (hereafter referred to as mitophagy), is essential for maintaining cardiac function. The molecular mechanism mediating mitophagy during pressure overload (PO) poorly understood. We have shown previously that in the heart mediated primarily by Atg5/Atg7-independent mechanisms, Unc-51-like kinase 1 (Ulk1)-dependent alternative mitophagy, myocardial ischaemia. Here, we investigated role PO-induced hypertrophy.
Acyl-coenzyme A (CoA)–binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular feedback regulator of autophagy. Here, we report that injection a monoclonal antibody neutralizing ACBP/DBI (α-DBI) protects the murine liver against ischemia/reperfusion damage, intoxication by acetaminophen and concanavalin A, nonalcoholic steatohepatitis caused methionine/choline-deficient diet well fibrosis induced bile duct ligation or carbon tetrachloride. α-DBI...
Abstract The molecular mechanisms by which FoxO transcription factors mediate diametrically opposite cellular responses, namely death and survival, remain unknown. Here we show that Mst1 phosphorylates FoxO1 Ser209/Ser215/Ser218/Thr228/Ser232/Ser243, thereby inhibiting FoxO1-mediated of proapoptotic genes. On the other hand, increases FoxO1-C/EBP-β interaction activates C/EBP-β phosphorylating it at Thr299, promoting prosurvival Myocardial ischemia/reperfusion injury is larger in...
Abstract CAV1/Caveolin1, an integral membrane protein, is involved in caveolae function and cellular signaling pathways. Here, we report that CAV1 a positive regulator of autophagy under oxidative stress cerebral ischemic injury. Treatment with hydrogen peroxide enhanced flux caused the localization BECN1 to mitochondria, whereas these changes were impaired absence CAV1. Among many signals, only LC3 foci formation response was abolished by deficiency. Under stress, interacted complex...
Caloric restriction mimetics (CRMs) are natural or synthetic compounds that mimic the health-promoting and longevity-extending effects of caloric restriction. CRMs provoke deacetylation cellular proteins coupled to an increase in autophagic flux absence toxicity. Here, we report identification a novel candidate CRM, namely 3,4-dimethoxychalcone (3,4-DC), among library polyphenols. When added several different human cell lines, 3,4-DC induced cytoplasmic stimulated flux. At difference with...
Autosis is a distinct form of cell death that requires both autophagy genes and the Na+,K+-ATPase pump. However, relationship between machinery unknown. We explored hypothesis interacts with protein Beclin 1 during stress autosis-inducing conditions. Starvation increased 1/Na+,K+-ATPase interaction in cultured cells, this was blocked by cardiac glycosides, inhibitors Na+,K+-ATPase. Increases were also observed tissues from starved mice, livers patients anorexia nervosa, brains neonatal rats...
Lysosomal dysfunction caused by mutations in lysosomal genes results storage disorder (LSD), characterized accumulation of damaged proteins and organelles cells functional abnormalities major organs, including the heart, skeletal muscle, liver. In LSD, autophagy is inhibited at degradation step autophagosomes observed. Enlargement left ventricle (LV) contractile were observed RagA/B cardiac-specific KO (cKO) mice, a mouse model LSD which acidification impaired irreversibly. YAP, downstream...
Transmembrane protein 9 (TMEM9) is a transmembrane that regulates lysosomal acidification by interacting with the v-type ATPase complex. However, role of TMEM9 in lysosome-dependent autophagy machinery has yet to be identified. In this study, we demonstrate TMEM9, which involved vesicle acidification, Rab9-dependent alternative through its interaction Beclin1. The cytosolic domain interacts Beclin1 via Bcl-2-binding domain. This between and dissociates Bcl-2, an autophagy-inhibiting partner,...
Autosis is a unique form of cell death with characteristic morphological and biochemical features caused by dysregulated autophagy. observed in the heart during late phase ischemia/reperfusion (I/R), when marked accumulation autophagosomes induced. We previously showed that excessive promotes autosis cardiomyocytes. Although inhibition autophagic flux via upregulation Rubicon induces I/R, it appears additional mechanisms exacerbating autophagosome are required for induction autosis. Here, we...
In neurodegenerative diseases like Alzheimer's disease (AD), tau is hyperphosphorylated and forms aggregates neurofibrillary tangles in affected neurons. Autophagy critical to clear the of disease-associated proteins often altered patients animal models AD. Because mechanistic target rapamycin (mTOR) negatively regulates autophagy hyperactive brains with AD, mTOR an attractive therapeutic for However, pharmacological strategies increase by targeting inhibition cause various side effects....